卒中后抑郁尿液代谢物标志物及机制 研究进展

Urinary Metabolite Biomarkers and Mechanisms in Post-Stroke Depression: A Literature Review

摘要: 卒中后抑郁(post-stroke depression, PSD)是卒中后常见而容易被低估的神经精神并发症，可影响康复参与、功能恢复、生活质量及长期预后。由于PSD诊断主要依赖量表和访谈，易受失语、认知障碍、疲劳、躯体症状重叠和文化表达差异影响，客观、无创、可重复的生物标志物研究具有重要价值。尿液代谢组学可通过检测小分子代谢物反映卒中后全身神经免疫代谢状态，具有非侵入、易重复采样和适合随访等优势。现有研究提示，乳酸、棕榈酸、壬二酸、酪氨酸、苯丙氨酸、甘油酸和假尿苷等代谢物可能与PSD相关；其背后主要涉及氨基酸代谢、脂质代谢、能量代谢、氧化应激及色氨酸–犬尿氨酸通路。其中，色氨酸经犬尿氨酸方向代谢后可生成具有神经活性的中间产物，可能通过5-羟色胺合成减少、谷氨酸能调节、氧化应激和胶质细胞活化参与情绪障碍发生。血浆代谢物、肠道菌群和神经炎症研究进一步提示PSD并非单纯心理反应，而是卒中后脑损伤、外周炎症、代谢重编程和肠脑轴异常共同作用的临床综合征。本文围绕PSD流行病学与诊断困境、尿液代谢组学优势、PSD尿液代谢物证据、主要代谢通路、交叉机制、研究局限和未来方向进行综述，以期为PSD客观评估和尿液标志物临床转化提供参考。

Abstract: Post-stroke depression (PSD) is a common and often under-recognized neuropsychiatric complication after stroke. It is associated with poor rehabilitation engagement, impaired functional recovery, reduced quality of life and adverse long-term outcomes. Because the diagnosis of PSD mainly relies on clinical scales and interviews, it may be affected by aphasia, cognitive impairment, fatigue, overlap of somatic symptoms and cultural differences in emotional expression. Therefore, objective, non-invasive and repeatable biomarkers are urgently needed. Urinary metabolomics provides a practical approach to monitoring small-molecule metabolites that reflect systemic neuroimmune and metabolic alterations after stroke. Current evidence suggests that lactate, palmitic acid, azelaic acid, tyrosine, phenylalanine, glyceric acid and pseudouridine may be candidate urinary biomarkers of PSD. The involved pathways mainly include amino acid metabolism, lipid metabolism, energy metabolism, oxidative stress and the tryptophan-kynurenine pathway. In particular, neuroactive metabolites generated along the kynurenine pathway may link reduced serotonin availability, glutamatergic modulation, oxidative stress and glial activation to depressive symptoms after stroke. Evidence from plasma metabolites, gut microbiota and neuroinflammation further indicates that PSD is not merely a psychological reaction to stroke, but a clinical syndrome shaped by brain injury, peripheral inflammation, metabolic reprogramming and gut-brain axis dysfunction. This review summarizes the epidemiology, clinical burden and diagnostic dilemma of PSD, the advantages of urinary metabolomics, chronological urinary metabolite evidence, major metabolic pathways, cross-mechanistic links, current limitations and future directions.